Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
11,262
result(s) for
"Longo, S"
Sort by:
Harrison's manual of medicine
This full color, portable guide covers all diseases and conditions commonly seen in general medical practice. This edition has been updated to reflect the latest clinical developments in medicine. Designed for quick access and employing an effective blend of concise text, bulleted key points, decision trees, and summary tables, the \"Manual\" makes it easy to find what you need at the point of care. -- From publisher's description.
Book
Vascular plant changes in extreme environments: effects of multiple drivers
The Antarctic Peninsula is one of three regions of the planet that have experienced the highest rates of climate warming over recent decades. Based on a comprehensive large-scale resurvey, allowing comparison of new (2009) and historical data (1960s), we show that the two native Antarctic vascular plant species have exhibited significant increases in number of occupied sites and percent cover since the 1960s: Deschampsia antarctica increasing in coverage by 191 % and in number of sites by 104 %. Colobanthus quitensis increasing in coverage by 208 % and number of sites by 35 %. These changes likely occurred in response to increases of 1.2 °C in summer air temperature over the same time period. Both species exhibited changes with elevation due to the interaction of multiple drivers (climatic factors and animal disturbance), producing heterogeneity of responses across an elevation gradient. Below an elevation of 20 m fur seal activity exerted negative impacts. Between 20 and 60 m, both plant species underwent considerable increases in the number of sites and percent cover, likely influenced by both climate warming and nutrient input from seals. Above an elevation threshold of 60 m the maximum elevation of the sites occupied decreased for both species, perhaps as a consequence of physical disturbance at higher elevations due to the permafrost conditions and/or the snow cover thickness and persistence. Understanding the role of disturbance drivers for vegetation change in cold regions may become a research priority to enable improved forecasting of biological responses and feedbacks of climate warming on ecosystems in these globally influential regions.
Journal Article
Fame
Passions will be tested and young hearts will be broken. Ultimately, talent, dedication and hard work will triumph. Centers around a group of dancers, singers, musicians and actors at the New York City High School of Performing Arts, and their spirited drive to live out their dreams of stardom. In an incredibly competitive atmosphere, each student must shine amidst the tumult of school work, deep friendships, budding romance and self-discovery.
DVD
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific antibody, named 10E8, which neutralizes ∼98% of tested viruses. An analysis of sera from 78 healthy HIV-1-infected donors demonstrated that 27% contained MPER-specific antibodies and 8% contained 10E8-like specificities. In contrast to other neutralizing MPER antibodies, 10E8 did not bind phospholipids, was not autoreactive, and bound cell-surface envelope. The structure of 10E8 in complex with the complete MPER revealed a site of vulnerability comprising a narrow stretch of highly conserved gp41-hydrophobic residues and a critical arginine or lysine just before the transmembrane region. Analysis of resistant HIV-1 variants confirmed the importance of these residues for neutralization. The highly conserved MPER is a target of potent, non-self-reactive neutralizing antibodies, suggesting that HIV-1 vaccines should aim to induce antibodies to this region of HIV-1 envelope glycoprotein.
A novel neutralizing antibody from a healthy HIV-1-infected donor that is specific for the membrane proximal region of gp41 is reported; the antibody has high potency and breadth, is not autoreactive and does not bind phospholipids.
Target for HIV/AIDS vaccine
Jinghe Huang
et al
. report a novel neutralizing antibody from a healthy HIV-1-infected donor that is specific for the membrane-proximal region of gp41. The antibody has high potency and breadth, is not autoreactive and does not bind phospholipids. This work demonstrates a conserved site of gp41 vulnerability that is an important target antigen for HIV neutralization, with implications for efforts to elicit broadly neutralizing antibodies with vaccines.
Journal Article
Experimental study on radial gravity currents flowing in a vegetated channel
We present an experimental study of gravity currents in a cylindrical geometry, in the presence of vegetation. Forty tests were performed with a brine advancing in a fresh water ambient fluid, in lock release, and with a constant and time-varying flow rate. The tank is a circular sector of angle $30^\\circ$ with radius equal to 180 cm. Two different densities of the vegetation were simulated by vertical plastic rods with diameter $D=1.6\\ \\textrm{cm}$. We marked the height of the current as a function of radius and time and the position of the front as a function of time. The results indicate a self-similar structure, with lateral profiles that after an initial adjustment collapse to a single curve in scaled variables. The propagation of the front is well described by a power law function of time. The existence of self-similarity on an experimental basis corroborates a simple theoretical model with the following assumptions: (i) the dominant balance is between buoyancy and drag, parameterized by a power law of the current velocity $\\sim |u|^{\\lambda-1}u$; (ii) the current advances in shallow-water conditions; and (iii) ambient-fluid dynamics is negligible. In order to evaluate the value of ${\\lambda}$ (the only tuning parameter of the theoretical model), we performed two additional series of measurements. We found that $\\lambda$ increased from 1 to 2 while the Reynolds number increased from 100 to approximately $6\\times10^3$, and the drag coefficient and the transition from $\\lambda=1$ to $\\lambda=2$ are quantitatively affected by D, but the structure of the model is not.
Journal Article
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1
Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.
Journal Article
miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance
MicroRNAs are predicted to regulate [almost equal to]30% of all human genes by targeting sequences in their 3' UTR. Polymorphisms in 3' UTR of several genes have been reported to affect gene expression, but the mechanism is not fully understood. Here, we demonstrate that 829C[rightward arrow]T, a naturally occurring SNP, near the miR-24 binding site in the 3' UTR of human dihydrofolate reductase (DHFR) affects DHFR expression by interfering with miR-24 function, resulting in DHFR overexpression and methotrexate resistance. miR-24 has a conserved binding site in DHFR 3' UTR. DHFR with WT and 3' UTR containing the 829C[rightward arrow]T mutation were expressed in DG44 cells that lack DHFR. Overexpression of miR-24 in cells with WT DHFR resulted in down-regulation of DHFR protein, whereas no effect on DHFR protein expression was observed in the mutant 3' UTR-expressing cells. Inhibition of endogenous miR-24 with a specific inhibitor led to up-regulation of DHFR in WT and not in mutant cells. Cells with the mutant 3' UTR had a 2-fold increase in DHFR mRNA half-life, expressed higher DHFR mRNA and DHFR protein, and were 4-fold more resistant to methotrexate as compared with WT cells. SNP-829C[rightward arrow]T, therefore, leads to a decrease in microRNA binding leading to overexpression of its target and results in resistance to methotrexate. We demonstrate that a naturally occurring miRSNP (a SNP located at or near a microRNA binding site in 3' UTR of the target gene or in a microRNA) is associated with enzyme overproduction and drug resistance.
Journal Article
Developmental Pathway of the MPER-Directed HIV-1-Neutralizing Antibody 10E8
Antibody 10E8 targets the membrane-proximal external region (MPER) of HIV-1 gp41, neutralizes >97% of HIV-1 isolates, and lacks the auto-reactivity often associated with MPER-directed antibodies. The developmental pathway of 10E8 might therefore serve as a promising template for vaccine design, but samples from time-of-infection-often used to infer the B cell record-are unavailable. In this study, we used crystallography, next-generation sequencing (NGS), and functional assessments to infer the 10E8 developmental pathway from a single time point. Mutational analysis indicated somatic hypermutation of the 2nd-heavy chain-complementarity determining region (CDR H2) to be critical for neutralization, and structures of 10E8 variants with V-gene regions reverted to genomic origin for heavy-and-light chains or heavy chain-only showed structural differences >2 Å relative to mature 10E8 in the CDR H2 and H3. To understand these developmental changes, we used bioinformatic sieving, maximum likelihood, and parsimony analyses of immunoglobulin transcripts to identify 10E8-lineage members, to infer the 10E8-unmutated common ancestor (UCA), and to calculate 10E8-developmental intermediates. We were assisted in this analysis by the preservation of a critical D-gene segment, which was unmutated in most 10E8-lineage sequences. UCA and early intermediates weakly bound a 26-residue-MPER peptide, whereas HIV-1 neutralization and epitope recognition in liposomes were only observed with late intermediates. Antibody 10E8 thus develops from a UCA with weak MPER affinity and substantial differences in CDR H2 and H3 from the mature 10E8; only after extensive somatic hypermutation do 10E8-lineage members gain recognition in the context of membrane and HIV-1 neutralization.
Journal Article
Gravity-driven flow of Herschel–Bulkley fluid in a fracture and in a 2D porous medium
New analytical models are introduced to describe the motion of a Herschel–Bulkley fluid slumping under gravity in a narrow fracture and in a porous medium. A useful self-similar solution can be derived for a fluid injection rate that scales as time
$t$
; an expansion technique is adopted for a generic injection rate that is power law in time. Experiments in a Hele-Shaw cell and in a narrow channel filled with glass ballotini confirm the theoretical model within the experimental uncertainty.
Journal Article
Ascending non-Newtonian long drops in vertical tubes
We report on theoretical and experimental studies describing the buoyancy-driven ascent of a Taylor long drop in a circular vertical pipe where the descending fluid is Newtonian, and the ascending fluid is non-Newtonian yield shear thinning and described by the three-parameter Herschel–Bulkley model, including the Ostwald–de Waele model as a special case for zero yield. Results for the Ellis model are included to provide a more realistic description of purely shear-thinning behaviour. In all cases, lubrication theory allows us to obtain the velocity profiles and the corresponding integral variables in closed form, for lock-exchange flow with a zero net flow rate. The energy balance allows us to derive the asymptotic radius of the inner current, corresponding to a stable node of the differential equation describing the time evolution of the core radius. We carried out a series of experiments measuring the rheological properties of the fluids, the speed and the radius of the ascending long drop. For some tests, we measured the velocity profile with the ultrasound velocimetry technique. The measured radius of the ascending current compares fairly well with the asymptotic radius as derived through the energy balance, and the measured ascent speed shows a good agreement with the theoretical model. The measured velocity profiles also agree with their theoretical counterparts. We have also developed dynamic similarity conditions to establish whether laboratory physical models, limited by the availability of real fluids with defined rheological characteristics, can be representative of real phenomena on a large scale, such as exchanges in volcanic conduits. Appendix B contains scaling rules for the approximated dynamic similarity of the physical process analysed; these rules serve as a guide for the design of experiments reproducing real phenomena.
Journal Article